B/25. Natural opiates, opioid receptors Flashcards
1
Q
Drugs need to know in this topic
A
Morphine Codein
2
Q
Endogenous opioid peptides
A
- β-endorphin 2. Enkephalin 3. Dynorphin
3
Q
opioid receptors
A
μ (mu) δ (delta) κ (kappa)
4
Q
Physiologic effects of opioids
A
Acute
- Analgesia (pain relief)
- Sedation (additive with other CNS depressants)
- Respiratory depression (desensitization of CO2 center)
- Antitussive action (suppression of cough reflux)
- Nausea and vomiting (stimulation of chemoreceptors in the area postrema)
- Intestinal motility ↓
- Circular smooth muscle contraction (urinary tract, biliary)
- Miosis (pupillary constriction)
- Histamine release, ADH release
Chronic
- Tolerance (pharmacodynamic tolerance; occurs to all effects except miosis and constipation)
- Dependence (physical and psychologic)
5
Q
Morphine
A
Strong agonist
Natural
- Analgesic use (post-operative pain, chronic pain syndromes, post-MI)
- Anesthesia
- Acute pulmonary edema
6
Q
Codeine
A
Weak agonist
Natural
- Antitussive
- Analgesic effect in combination with NSAID’s or acetaminophen
*NE and 5-HT reuptake inhibition (dextromethorphan)
7
Q
Pharmacokinetic properties
A
- Hepatic metabolism by CYP450 enzymes
- Morphine is metabolized into an intermediate compound (morphine-6-glucoronide), which has much higher activity than the original compound; elevated serum levels (as in renal impairment) may cause life-threatening toxicity
- Excretion via the kidneys
- Alcohol increases opioid peak concentration in serum
- T1/2 → short-acting (1-2 h’), intermediate-acting (6-8 h’), long-acting (24 h’)
8
Q
Adverse effects and toxicity
A
- Constipation (may cause paralytic ileus in severely high doses)
- Biliary colic
- Sedation and CNS depression (dose-dependent effect, additive with other CNS depressants)
- Opioid-induced hyperalgesia – nociceptive sensitization caused by long-term exposure to opioids
- ‘Psuedo-allergy’ – IgE-independent mast cell degranulation (histamine release induces rash, wheezing, tachycardia)
9
Q
Acute toxicity
A
Presentation (classic triad):
- Pupillary constriction (‘pinpoint pupils’)
- Respiratory depression
- Coma
Management:
- IV Naloxone
- Supportive
10
Q
Dependence
A
- *Withdrawal presentation (abstinence syndrome):**
1. Yawning
2. Increased secretion: lacrimation, rhinorrhea, salivation
3. Anxiety, sweating, hyperthermia
4. Muscle cramps, spasm, CNS-originating pain
5. Piloerection
Management:
1. Methadone, Buprenorphine, Naltrexone
2. Clonidine
3 Supportive
11
Q
Teratogenicity
A
- Respiratory depression
- Preeclampsia
- Fetal death
- Physical dependence → ‘Neonatal abstinence syndrome